N-Methyl Amisulpride Shows Short-Term Efficacy in Acute Schizophrenia in Phase 2 Trial
USA: An investigational benzamide antipsychotic, N-methyl amisulpride, demonstrated significant symptom improvement in hospitalized adults with schizophrenia in a phase II randomized trial. This agent is structurally related to amisulpride but differs in dosing profile and side-effect characteristics. However, the study’s short duration of 4 weeks limits conclusions regarding long-term efficacy and durability of treatment response.
A new study published in JAMA Psychiatry provides further evidence on the potential of LB-102 (N-methyl amisulpride), a novel antipsychotic agent targeting dopamine D2/D3 and serotonin 5-HT7 receptors, for the treatment of acute schizophrenia. The trial, led by Anna Eramo and colleagues, evaluated the drug’s efficacy, safety, and tolerability in adults experiencing acute psychotic episodes.
The phase II, multicenter, double-blind, placebo-controlled trial enrolled 359 adults aged 18 to 55 years who required hospitalization due to worsening schizophrenia symptoms. Participants were randomized to receive once-daily oral doses of LB-102 at 50 mg, 75 mg, or 100 mg, or a placebo, over a 4-week inpatient treatment period. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score, a widely used measure of schizophrenia symptom severity. Secondary endpoints included changes in Clinical Global Impressions–Severity (CGI-S) scores and other symptom domains.
The trial revealed the following findings:
- LB-102 at doses of 50 mg and 75 mg showed statistically significant improvements in PANSS total scores compared to placebo.
- The 100 mg dose also demonstrated symptom improvement, although it was not included in the primary statistical testing hierarchy.
- Benefits were observed across multiple secondary endpoints, including both positive and negative symptoms.
- Findings indicate a broad therapeutic effect of LB-102 in acute schizophrenia.
- LB-102 was generally well tolerated across all dose groups.
- The rate of treatment-emergent adverse events was similar between LB-102 and placebo groups.
- No major safety concerns were identified during the trial.
- The incidence of extrapyramidal symptoms was notably low.
- Prolactin-related adverse effects were observed but occurred infrequently.
- Weight gain was minimal, suggesting a manageable metabolic profile.
- A few participants discontinued treatment due to adverse events.
- Serious adverse events were rare across all groups.
- One death occurred in the placebo group.
- Some reported adverse events, such as insomnia and anxiety, were present at baseline, indicating they may reflect underlying disease symptoms rather than drug-related effects.
Despite encouraging results, the study has limitations. Its 4-week duration limits evaluation of long-term efficacy and safety. The inpatient setting may not reflect real-world conditions, and the lack of an active comparator restricts comparison with existing therapies.
Overall, LB-102 demonstrated meaningful symptom improvement with a favorable short-term safety profile in adults with acute schizophrenia, supporting the need for larger and longer-term studies to confirm its clinical role.
Reference:
Eramo A, Correll CU, Walling DP, et al. Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adults With Acute Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. Published online April 22, 2026. doi:10.1001/jamapsychiatry.2026.0428
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